Is CELSR1 p.Ser704= (c.2112C>T) pathogenic?

CELSR1 p.Ser704= (c.2112C>T) is classified Likely benign in CELSR1 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2022-07-28). Ultra-rare (popmax 0.028%, afr); Associated with CELSR1-related disorder.

What condition is associated with CELSR1 p.Ser704= (c.2112C>T)?

CELSR1 p.Ser704= (c.2112C>T) is associated with CELSR1-related disorder (ClinVar).

How common is CELSR1 p.Ser704= (c.2112C>T) in the general population?

CELSR1 p.Ser704= (c.2112C>T) is ultra-rare (popmax 0.028%, afr) (gnomAD).

CELSR1 p.Ser704=

c.2112C>T · rs145293715 · VCV3029626

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.028%, afr)

Conditions

CELSR1-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.05	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.7	GERP 0.59, phastCons 1
Overall
CADD	12.19	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.028% African / African-American · 21/74,906 alleles

Filtering AF 0.0188% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0157%

Overall 0.00136% 22/1,612,372 alleles · ultra-rare exomes 10/1,460,232 · genomes 12/152,140 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.028%	3,567
South Asian	0.0011%	91,090

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: CELSR1
Protein: p.Ser704=
Coding: c.2112C>T
MANE Select: NM_001378328
dbSNP: rs145293715
Type: single nucleotide variant
Location: chr22:46535059 (GRCh38)
Gene constraint: LOEUF 0.564 · pLI <0.01 (gnomAD)
Residue 704: a UniProt-annotated variant site (in lmphm9); the cadherin 5 domain

Full CELSR1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

CELSR1-related disorder

Similar variants

CELSR1 p.Arg1643Gln Uncertain significance ★★ ⚠ same condition
CELSR1 p.Pro46His Uncertain significance ★★ ⚠ same condition
CELSR1 p.Ser2825Leu Uncertain significance ★★ same condition
CELSR1 p.Val2338Ile Uncertain significance ★★ ⚠ same condition
CELSR1 p.Leu979Phe Likely pathogenic ★ ⚠ same condition
CELSR1 p.Ala2486Pro Uncertain significance ★ same condition
CELSR1 p.Asp1201Asn Conflicting classifications of pathogenicity ★ same condition
CELSR1 p.Cys1934= Uncertain significance ★ same condition

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/celsr1-p-ser704 (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown